HORMONAL-CONTROL OF GROWTH IN THE GENETICALLY-OBESE ZUCKER RAT .1. LINEAR GROWTH, PLASMA INSULIN-LIKE GROWTH FACTOR-I (IGP-I) AND IGF-BINDING PROTEINS
body-composition; developmental-changes; Endocrinology & Metabolism; expression; gh; hepatocytes; messenger-rna; radioimmunoassay; secretion; serum; somatomedin-c
The genetically obese Zucker rat is a widely used model of early-onset obesity. Like obese children, these obese rats are hyperinsulinemic and have low GH secretion. However, data on linear growth and insulin-like growth factor-I (IGF-I) levels in this model are scanty and contradictory. In the present study, we investigated linear growth and its hormonal control in Zucker rats (male and female) from 4-20 weeks of age. In the obese animals, compared to their lean littermates, the naso-anal length was normal or slightly greater, whereas the tails and femurs were shorter. The plasma concentration of IGF-I increased between 4-20 weeks of age, and IGF-I levels were normal or slightly higher in the obese animals. The serum level of IGF-binding protein-3 (IGFBP-3) measured by Western ligand blotting was not significantly different in lean vs, obese rats. To assess the IGF-I response to GH, bovine GH was administered (250 mu g/100 g BW, ip, daily for 3 days) to 16- to 20-week-old female Zucker rats; plasma IGF-I concentrations increased more in the obese (percent increase over baseline, 347 +/- 44% vs. 194 +/- 31%; P < 0.01). These results show that despite low GH secretion, genetically obese Zucker rats have 1) normal linear (nasoanal) growth, 2) normal or increased circulating levels of IGF-I and IGFBP-3, and 3) increased plasma IGF-I responses to exogenous GH. These results suggest that the GH-independent growth in this model could result from direct effects of hyperinsulinism on circulating IGF-I and IGFBP-3 levels and/or indirect effects through increased GH receptor function.
Nguyenyamamoto L; Deal C L; Finkelstein J A; Vanvliet G
Endocrinology
1994
1994-03
Journal Article
<a href="http://doi.org/10.1210/en.134.3.1382" target="_blank" rel="noreferrer noopener">10.1210/en.134.3.1382</a>
TAMOXIFEN AND ESTROGEN LOWER CIRCULATING LIPOPROTEIN(A) CONCENTRATIONS IN HEALTHY POSTMENOPAUSAL WOMEN
binding-proteins; breast-cancer; cardiovascular risk-factors; Cardiovascular System & Cardiology; coronary heart-disease; estrogen replacement; growth factor-i; insulin-like growth factor i; lipoprotein(a); lp(a) lipoprotein; menopause; replacement therapy; serum lipoprotein(a); smooth-muscle cells; somatomedin-c; tamoxifen; therapy
Data in the literature suggest that circulating levels of lipoprotein(a) [Lp(a)] and insulinlike growth factor I (IGF-I) respond similarly to therapy with growth hormone, estrogen, or tamoxifen. To more clearly document these relations, we designed a randomized, double-blind, placebo-controlled study of the effects of tamoxifen and continuous estrogen on circulating levels of Lp(a), IGF-I, and IGF binding protein 3 (IGFBP-3) in healthy postmenopausal women. Both estrogen and tamoxifen decreased serum levels of IGF-I to 30% below baseline during the 3 months of treatment, while IGFBP-3 levels were unchanged. Plasma Lp(a) levels decreased to 24% below baseline after 1 month of treatment with either estrogen or tamoxifen (P < .05 for estrogen only); after 3 months Lp(a) decreased to 34% below baseline with tamoxifen therapy (P < .05) but returned to only 16% below baseline with estrogen. The correlation between Lp(a) and IGF-I was highly significant (P < .0001). We conclude that (1) tamoxifen lowers plasma Lp(a) levels in healthy postmenopausal women, (2) the suppressive effects of tamoxifen and estrogen on circulating Lp(a) concentration diverge after the first month of therapy, and (3) circulating levels of Lp(a) and IGF-I are strongly correlated with each other, an indication that they may share regulatory influences.
Shewmon D A; Stock J L; Rosen C J; Heiniluoma K M; Hogue M M; Morrison A; Doyle E M; Ukena T; Weale V; Baker S
Arteriosclerosis and Thrombosis
1994
1994-10
Journal Article
<a href="http://doi.org/10.1161/01.atv.14.10.1586" target="_blank" rel="noreferrer noopener">10.1161/01.atv.14.10.1586</a>